Abstract

The first theoretical investigation on NHC-catalyzed [4+1] cyclization of (Z)-N′-hydroxybenzimidamide and p-chlorobenzaldehyde was provided by our DFT calculation. Via deprotonation of triazole salt precursor, the free N-Heterocyclic Carbene (NHC) catalyst was initially generated. Then, via rapid carbene addition to aldehyde followed by proton transfer, the breslow intermediate was afforded and further converted to acyl azolium under oxidation acting as electrophile in the following. Subsequently, with additional amidoxime, the nucleophilic substitution occurs with its nucleophile group leading to ester intermediate. After elimination of recovered HNHC, ester undergoes aza-ring closure and dehydration to construct five-membered aromatic heterocyclic structure of target 3,5-disubstituted 1,2,4-oxadiazole product. The proton transfer affording breslow intermediate of step 3 is determined to be rate-limiting for the whole process.

Keywords:[4 + 1] cyclization; Amidoxime; 1,2,4-oxadiazole; Triazole salt; N-heterocyclic carbene